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Scientists discover key gene in artery formation

A group of scientists at the NIH have discovered that the phospholipase C gamma-1 protein called Plcg1 for short is required for the formation of arteries in zebrafish embryos. This finding by Dr. Nathan Lawson and colleagues provides the first in vivo evidence of a role for Plcg1 in arterial development, and lends important new insight into the developmental cues that specify arteries versus veins.

The report is published in the June 1st issue of Genes & Development.

During embryogenesis, a population of cells, called endothelial cells, give rise to the vascular and lymphatic system. Extensive research into the genetic basis of vascular development has revealed a crucial and evolutionarily conserved role for the vascular endothelial growth factor (Vegf) signaling pathway in determining endothelial cell fate. However, the genes that dictate venous versus arterial cell fate remain largely unknown.

As Dr. Lawson explains, "Until recently, we really didn't know what the signals were that determined artery and venous identity, or even that this process was governed by genetic signals. It was always thought that circulatory flow and pressure caused a blood vessel to be an artery or a vein. But our work, along with studies in mouse, demonstrates that this identification step is crucial for normal blood vessel formation."

This work by Dr. Lawson and colleagues in Brant Weinstein's lab at the National Institutes of Health (Bethesda, MD) reveals that Plcg1 functions downstream of Vegf in vivo to coax endothelial cells into adopting an arterial fate.

Dr. Lawson and colleagues conducted their studies in zebrafish (an established vertebrate model organism) that were genetically engineered to have fluorescent blood vessels. Since zebrafish embyos are normally transparent, the fluorescing blood vessels enabled the scientists to easily observe vessel formation during development. To identify potential regulators of Vegf signaling, Dr.
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Contact: Heather Cosel
coselpie@cshl.org
Cold Spring Harbor Laboratory
31-May-2003


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